The acquired immunodeficiency syndrome (AIDS) is a global pandemic with over 14 million human immunodeficiency virus (HIV)-infected individuals worldwide. A major focus within our laboratory has been on defining the unique epidemiologic, clinical, virologic, and immunologic features of HIV-1 and HIV-2 infections in developing countries and in the U.S. In Pune, India, we established a prospective cohort of over 2,000 high-risk individuals attending STD clinics, of whom 25% were seropositive for HIV- 1. Over a 4-year time period, seroprevalence rose among commercial sex workers from 7.3% to 44%. Phylogenetic analysis of viral strains isolated from these individuals demonstrates both clade B and C strains with high-titer neutralizing antibody against clade B isolates. In Lagos, Nigeria, we documented a rising seroprevalence of both HIV-1 and HIV-2 among female prostitutes with a strong correlation with genital ulcer disease. Additional studies among STD patients in Baltimore demonstrated the low usage rate of condoms and a high rate of recidivism for STDs. There was a high incidence of HIV infection among these individuals. In perinatal studies of over 500 children born to HIV- infected women in Zaire, Haiti, Malawi, and the U.S., we documented a 28% perinatal transmission rate which correlated with depressed maternal CD4 and elevated CD8 lymphocyte counts, anemia, p24 antigenemia, chorioamnionitis, and funisitis. In addition, perinatal transmission appeared to correlate with elevated concentration of IgG-1 antibodies to the V3 loop in mothers, and with elevated levels of p24 antigen and secretory IgA to gp160 in cervical-vaginal secretions of transmitting mothers. Approximately 3% of infected children may have become infected postnatally from breastfeeding, and virologic studies demonstrated HIV DNA and p24 antigen in 50-70% of breast milk specimens within the first week following delivery. In studies of HTLV infection, we documented a 15.4% perinatal transmission rate of HTLV-1 with an increased risk of transmission in women co-infected with HIV-1. In a prospective study of HIV and HTLV co-infection in Brazil, we documented elevated CD4 lymphocytes, beta-2-microglobulin, and p24 antigen level among dually infected individuals. Further studies are planned to elucidate the immunologic modulations of HIV infection by co-infection with HTLV in these cohorts.